PROJECT SUMMARY This is an R24 application to support the infrastructure of our environmental epidemiology cohort, Nurses? Health Study 3 (NHS3), an open, prospective, web-based cohort (www.nhs3.org). Participants are residence of the United States and Canada born after 1965. Most of the female participants (89%) have enrolled before menopause and 41% of female participants and 62% of male participants have no prior pregnancy history. In this innovative web-based study, we have been collecting detailed information on personal characteristics and potential disease risk factors every 6 months, including diet, physical activity, psychosocial factors, and a wide variety of occupational and environmental exposures. Data collection has focused on current exposures, as well as those experienced during adolescence, prior to first pregnancy, and during pregnancy. Discoveries made in NHS3 will build on the knowledge and experience gained from earlier cohorts on the impacts of the environment on chronic disease risk, but takes advantage of modern technology to collect novel prospective data during important windows of exposure across the life course. The NHS3 investigators have substantial experience in environmental epidemiology, exposure assessment, and Big Data analytics, as well as in managing and maintaining large prospective cohort studies. This cohort provides a unique opportunity to address key outstanding questions in environmental epidemiology, by collecting highly detailed information on multiple environmental exposures at key points in the life course. Here, we propose to support infrastructure activities in the expanded NHS3 cohort that maximize the existing resources and broaden the current scope of research, to allow the investigation of multiple environmental exposures. We will focus our efforts in three main areas: 1) the expansion of study operations and maximization of existing resources, 2) the collection of environmental exposure samples, and 3) expansion of web-based mobile technologies and assessment of spatial uncertainty and measurement error.